BACKGROUND:Rev-erbα is involved in the regulation of inflammation,but pharmacological activation of Rev-erbα increases the risk for cardiovascular diseases.To reduce the relevant risk,an exploration on SR9009,a Rev-erbα agonist,combined with other drugs to relieve inflammation in skeletal myoblasts was conducted,laying the theoretical foundation for the treatment of inflammation-associated skeletal muscle atrophy. OBJECTIVE:To investigate the relationship of SR9009,indolepropionic acid and nuclear factor-κB signaling pathways in lipopolysaccharide-induced C2C12 myoblasts. METHODS:(1)C2C12 myoblasts were induced to differentiate in the presence of lipopolysaccharide(1 μg/mL).RNA-seq and KEGG pathway analysis were used to study signaling pathways.(2)C2C12 myoblast viability was assessed using the cell counting kit-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,cells were categorized into control group,lipopolysaccharide(1 μg/mL)group,SR9009(10 μmol/L)+lipopolysaccharide group,indolepropionic acid(80μmol/L)+lipopolysaccharide group,and SR9009+indolepropionic acid+lipopolysaccharide group.ELISA was employed to measure protein expression levels of interleukin-6 in the cultured supernatant.Real-time quantitative PCR were employed to measure mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Western blot assay were employed to measure protein expression levels of NF-κB p65 and p-NF-κB p65.(3)After Rev-erbα was knocked down by siRNA,knockdown efficiency was assessed by RT-qPCR.And mRNA levels of interleukin-6 and tumor necrosis factor α were also measured. RESULTS AND CONCLUSION:Compared with the blank control group,lipopolysaccharide time-dependently inhibited myofibroblast fusion to form myotubes,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were elevated,and the level of interleukin-6 in the cell supernatant was significantly increased.The results of KEGG pathway showed that the nuclear factor-κB signaling pathway was activated by lipopolysaccharide.Indolepropionic acid exhibited significant suppression of C2C12 myoblasts viability when its concentration exceeded 80 μmol/L.Indolepropionic acid and SR9009 inhibited the activation of NF-κB signaling pathway,thereby played an anti-inflammatory role,and suppressed the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Compared with the lipopolysaccharide group,the ratio of p-NF-κB p65/NF-κB p65 protein expression were downregulated.SR9009 combined with indolepropionic acid notably reduced lipopolysaccharide-induced inflammation,further downregulated the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.The ratio of p-NF-κB p65/NF-κB p65 protein expression was significantly lower than that in the SR9009+lipopolysaccharide group or indolepropionic acid+lipopolysaccharide group.Rev-erbα increases time-dependently with lipopolysaccharide induction.The knockdown efficiency of Rev-erbα by siRNA reached over 58%,and lipopolysaccharide was added after Rev-erbα was successfully knocked down.Compared with the lipopolysaccharide group,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were significantly up-regulated.These results conclude that Rev-erbα may act as a promising pharmacological target to reduce inflammation.SR9009 targeted activation of Rev-erbα combined with indolepropionic acid significantly inhibits the nuclear factor-κB signaling pathway and attenuates the inflammatory response of C2C12 myofibroblasts.Moreover,the combined anti-inflammatory effect is superior to that of the intervention alone.

OBJECTIVES: To investigate the changes in blood levels of calcium and bone metabolism biochemical markers in patients with primary osteoporosis receiving treatment with denosumab. METHODS: Seventy-three patients with primary osteoporosis treated in our Department between December, 2021 and December 2023 were enrolled. All the patients were treated with calcium supplements, vitamin D and calcitriol in addition to regular denosumab treatment every 6 months. Blood calcium, parathyroid hormone (PTH), osteocalcin (OC), type I procollagen amino-terminal propeptide (PINP), and type I collagen carboxy-terminal telopeptide β special sequence (β‑CTX) data before and at 3, 6, 9, and 12 months after the first treatment were collected from each patient. RESULTS: Three months after the first denosumab treatment, the bone turnover markers (BTMs) OC, PINP, and β-CTX were significantly decreased compared to their baseline levels by 39.5% (P<0.001), 56.2% (P<0.001), and 81.8% (P<0.001), respectively. At 6, 9, and 12 months of treatment, OC, PINP, and β-CTX remained significantly lower than their baseline levels (P<0.001). Blood calcium level was decreased (P<0.05) and PTH level increased (P<0.05) significantly in these patients at months of denosumab treatment, but their levels were comparable to the baseline levels at 6, 9, and 12 months of the treatment (P>0.05). CONCLUSIONS Denosumab can suppress BTMs and has a good therapeutic effect in patients with primary osteoporosis, but reduction of blood calcium and elevation of PTH levels can occur during the first 3 months in spite of calcium supplementation. Blood calcium and PTH levels can recover the baseline levels as the treatment extended, suggesting the importance of monitoring blood calcium and PTH levels during denosumab treatment.
Humans ; Denosumab/therapeutic use* ; Calcium/blood* ; Parathyroid Hormone/blood* ; Biomarkers/blood* ; Osteoporosis/blood* ; Osteocalcin/blood* ; Procollagen/blood* ; Female ; Collagen Type I/blood* ; Peptide Fragments/blood* ; Bone Density Conservation Agents/therapeutic use* ; Bone and Bones/metabolism* ; Male ; Middle Aged ; Vitamin D ; Peptides/blood* ; Aged

Objective To investigate the correlations of CALLY index in early pregnancy with the onset and severity of preeclampsia.Methods A total of 987 pregnant women were prospectively en-rolled as study subjects,with 42 lost during follow-up,resulting in a final inclusion of 945 subjects.Based on the occurrence and severity of preeclampsia during follow-up,the pregnant women were di-vided into preeclampsia group(n=47),severe preeclampsia group(n=49),and normal group(n=849).General information and laboratory test results were collected from all pregnant women,and the CALLY index was calculated.The Pearson correlation analysis was used to explore the correlation be-tween CALLY index and severity of preeclampsia(mean arterial pressure);the receiver operating characteristic(ROC)curve was plotted to analyze the predictive efficacy of each indicator for pre-eclampsia;Cox regression analysis was used to explore the influencing factors for the onset of preeclamp-sia.Results The mean arterial pressure and 24-hour urine protein levels were higher in the severe pre-eclampsia group than those in the preeclampsia group and normal group,and higher in the preeclampsia group than those in the normal group(P＜0.05).The CALLY index was lower in the severe preeclamp-sia group than in the preeclampsia group and normal group,and lower in the preeclampsia group than in the normal group(P＜0.05).Pearson correlation analysis showed a negative correlation between CALLY index and mean arterial pressure(r=-0.571,P＜0.001).The ROC curve showed that the area under the curve(AUC)of CALLY index for predicting preeclampsia was 0.941(95％CI,0.900 to 0.981).Multivariate Cox regression analysis showed that an increased CALLY index was an independent protective factor for the onset of preeclampsia(HR=0.185,95％CI,0.092 to 0.374,P＜0.001).Conclusion The CALLY index is negatively correlated with the severity of preeclampsia and is an independent influencing factor for the onset of preeclampsia,which can be used as an auxiliary indicator to assess the onset and severity of preeclampsia in pregnant women.

Objective To analyze the differences in oral hygiene and oral microbiota between the patients with schizophrenia and healthy individuals in Baoshan City.Methods 26 patients with schizophrenia from Baoshan Third People's Hospital were selected as the SCZ group and 26 healthy individuals matched by age and BMI as the HC(Healthy control)group.Demographic data,physical indicators,and oral conditions were collected.Saliva samples from 52 subjects were collected and 16S rDNA gene sequencing was used to compare the differences in oral hygiene and oral microbiota between the patients with schizophrenia and the healthy individuals.Results The difference in oral microbial community richness between the SCZ group and the HC group was statistically significant(P<0.05),with the SCZ group containing higher species than the HC group;at the genus level,except for Fusobacterium in the SCZ group and Actinomyces in the HC group,the top 5 dominant bacterial species in both groups were consistent;the results of species difference analysis showed that Fusobacterium and Campylobacter in the SCZ group were higher than those in the HC group(P<0.05).Conclusion The partial dominant bacterial species in the oral cavity of the patients with schizophrenia have changed to sulfate-reducing bacteria that produce hydrogen sulfide.Excessive production of hydrogen sulfide or polysulfide may damage the energy metabolism of mitochondria.

BACKGROUND:At present,there are some limitations in evaluating the severity of acute spinal cord injury,and a rapid and accurate evaluation method is urgently needed. OBJECTIVE:To analyze the correlation between the expression levels of serum oxidative stress and nerve injury indexes and the severity of the disease in patients with acute spinal cord injury. METHODS:A total of 65 patients were included in the study from August 2020 to May 2022,including 32 patients in the experimental group(acute spinal cord injury)and 33 patients in the control group(simple spinal fracture).American Spinal Injury Association(ASIA)Impairment Scale and neurological function score were evaluated within 8 hours of admission.Meanwhile,serum levels of superoxide dismutase,malondialdehyde,glutathione,nitric oxide,glial fibrillary acidic protein and neuron-specific enolase were detected and compared between the two groups.The correlation between the expression levels of the above serological indicators in serum and ASIA impairment grade and AISA neural function score was analyzed. RESULTS AND CONCLUSION:The average serum levels of superoxide dismutase and glutathione in the experimental group were significantly lower than those of the control group(P<0.001),while the average serum levels of malondialdehyde,nitric oxide,glial fibrillary acidic protein and neuron-specific enolase in the experimental group were higher than those of the control group(P<0.01).The serum levels of superoxide dismutase and glutathione in the experimental group were positively correlated with the damage grade of AISA(r=0.862 4,0.849 3,P<0.01),while the serum levels of malondialdehyde,nitric oxide,glial fibrillary acidic protein and neuron-specific enolase were negatively correlated with the damage grade of AISA(r=-0.866 1,-0.638 1,-0.746 6,P<0.001),and the serum level of nitric oxide was not significantly correlated with the damage grade of AISA(r=-0.177 5,P>0.05).The serum level of glutathione in the experimental group was positively correlated with AISA sensory function scores(r=0.569 9,P<0.001),while the serum levels of malondialdehyde,glial fibrillary acidic protein and neuron-specific enolase were negatively correlated with AISA sensory function scores(r=-0.574 1,-0.099 2,-0.708 6,P<0.05),and the serum levels of superoxide dismutase and nitric oxide were not significantly correlated with AISA sensory function scores(r=0.230 8,-0.376 2,P>0.05).The serum levels of superoxide dismutase and glutathione in the experimental group were positively correlated with ASIA motor function scores(r=0.380,0.524 7,P<0.05);the serum levels of malondialdehyde,glial fibrillary acidic protein and neuron-specific enolase were negatively correlated with AISA motor function scores(r=-0.577 9,-0.452 2,-0.662 8,P<0.05);and the level of nitric oxide had no significant correlation with AISA motor function scores(r=-0.049 7,P>0.05).To conclude,the serum levels of superoxide dismutase,malondialdehyde,glutathione,nitric oxide,glial fibrillary acidic protein and neuron-specific enolase in serum of patients with acute spinal cord injury are significantly correlated with ASIA impairment grade and ASIA neural function score,which could be used as biomarkers for early clinical assessment of disease severity.

In the past decades, significant progress has been achived in cartilage regeneration. The traditional techniques for constructing tissue engineering cartilage scaffold mainly include pore agent method (or template method), phase separation method, gas foaming method, freeze-drying method, electrospinning method, etc. Cartilage is heterogeneous, and it is difficult for traditional scaffolds to simulate the high anisotropy of cartilage. Therefore, functional regeneration of cartilage is challenging. With the progress of three-dimensional(3D) printing technology, it is possible to prepare functional bionic scaffolds with fine structure and gradient changes through co-deposition of biomaterials, cells and active biomolecules, so as to achieve functional cartilage regeneration. This article reviewed 3D printing technology of cartilage tissue engineering, and the application of 3D printing technology in cartilage regeneration at different anatomical positions (articular cartilage, auricle cartilage, nasal cartilage). In addition, the importance of preparing bionic constructs with regional structure gradient and regional composition gradient was discussed. 3D bioprinting technology, 4D printing techniques, smart biomaterials brought hope for the construction of bionic tissues and organs.

This article has found that acupuncture can treat vascular cognitive impairment (VCI) through alleviating nerve cell apoptosis, enhancing hippocampal synaptic plasticity, improving hippocampal mitochondrial function, reducing brain inflammation, inhibiting oxidative stress response, protecting the blood-brain barrier, promoting angiogenesis, improving cerebral circulation, enhancing default network connectivity in brain regions, and improving white matter damage. At present, it is still in the preliminary stage to explore the mechanism of acupuncture treatment of VCI from the perspective of brain network connection. The existing mechanism researches mostly use electroacupuncture as an intervention method, and the selection of acupoints and the intensity of electroacupuncture stimulation are different. It is necessary to improve the rigor of the experiment, strengthen the study of conventional acupuncture, and explore the operation methods and needle retention time. The existing animal models lack consideration of other complications of VCI, and there are still some differences with the clinical characteristics of VCI patients, which need to be optimized in the future.

In the past decades, significant progress has been achived in cartilage regeneration. The traditional techniques for constructing tissue engineering cartilage scaffold mainly include pore agent method (or template method), phase separation method, gas foaming method, freeze-drying method, electrospinning method, etc. Cartilage is heterogeneous, and it is difficult for traditional scaffolds to simulate the high anisotropy of cartilage. Therefore, functional regeneration of cartilage is challenging. With the progress of three-dimensional(3D) printing technology, it is possible to prepare functional bionic scaffolds with fine structure and gradient changes through co-deposition of biomaterials, cells and active biomolecules, so as to achieve functional cartilage regeneration. This article reviewed 3D printing technology of cartilage tissue engineering, and the application of 3D printing technology in cartilage regeneration at different anatomical positions (articular cartilage, auricle cartilage, nasal cartilage). In addition, the importance of preparing bionic constructs with regional structure gradient and regional composition gradient was discussed. 3D bioprinting technology, 4D printing techniques, smart biomaterials brought hope for the construction of bionic tissues and organs.

Objective:To investigate the clinical effect and safety of camrelizumab combined with induction chemotherapy followed by concurrent chemoradiotherapy for patients with locally advanced nasopharyngeal carcinoma (NPC).Methods:A total of 24 patients with stage Ⅲ-IV A NPC were recruited prospectively to receive two cycles of camrelizumab combined with induction chemotherapy (docetaxel 75 mg/m 2+ cisplatin 25 mg/m 2 for three consecutive days) followed by concurrent chemoradiotherapy (prescription doses: 6 996 cGy in 33 fractions for PGTV and PGTV nd, 6 006 cGy in 33 fractions for PTV 1, 5 096 cGy in 28 fractions for PTV 2, and concurrent cisplatin chemotherapy with a dose of 75 mg/m 2). The short-term efficacy and adverse reactions were evaluated. Results:After induction therapy, nasopharyngeal lesions showed an objective response rate (ORR) of 91.6%, including 45.8% of complete response (CR) and 45.8% of partial response (PR); cervical lymph nodes showed an ORR of 95.8% (CR: 4.2%; PR: 91.6%). Seventeen patients accepted a reexamination under a nasopharyngoscope, and the biting biopsy result indicated that 13 patients among them had complete pathologic response. After concurrent chemoradiotherapy, nasopharyngeal lesions and cervical lymph nodes showed CR rates of 83.3% and 91.7% and PR rates of 16.7% and 8.3%, respectively. After the induction therapy, 13 patients with stage IV A NPC had ORR (PR) rates of 92.4% and 92.4%, respectively, at nasopharyngeal lesions and cervical lymph nodes. After concurrent chemoradiotherapy, the patients with stage IV A NPC had CR rates of 84.6% and 92.3% and PR rates of 15.4% and 7.7%, respectively, at nasopharyngeal lesions and cervical lymph nodes. Major adverse reactions include leukopenia, granulopenia, anemia, radioactive acute oropharyngeal mucositis and dermatitis, digestive tract reaction, fatigue, hypothyroidism, aminotransferase elevation, and reactive capillary hyperplasia. Conclusions:Camrelizumab combined with induction chemotherapy followed by concurrent chemoradiotherapy can achieve high short-term efficacy for patients with locally advanced nasopharyngeal carcinoma, without increasing the incidence of adverse reactions. Its long-term efficacy deserves further research.

OBJECTIVES: Clinically, it has been found that some patients with epilepsy are accompanied by cerebellar atrophy that is inconsistent with symptoms, but the pattern of cerebellar atrophy after epilepsy and the role of cerebellar atrophy in the mechanism of epilepsy have not been elucidated. This study aims to explore the specific pattern of cerebellar atrophy after epilepsy via analyzing magnetic resonance images in patients with postepileptic cerebellar atrophy. METHODS: A total of 41 patients with epilepsy, who received the treatment in Xiangya Hospital of Central South University from January 2017 to January 2022 and underwent cranial MRI examination, were selected as the case group. The results of cranial MRI examination of all patients showed cerebellar atrophy. In the same period, 41 cases of physical examination were selected as the control group. General clinical data and cranial MRI results of the 2 groups were collected. The maximum area and signal of dentate nucleus, the maximum width of the brachium pontis, the maximum anterior-posterior diameter of the pontine, and the maximum transverse area of the fourth ventricle were compared between the 2 groups. The indexes with difference were further subjected to logistic regression analysis to clarify the characteristic imaging changes in patients with cerebellar atrophy after epilepsy. RESULTS: Compared with the control group, the maximum width of the brachium pontis and the maximum anterior-posterior diameter of the pontine were decreased significantly, the maximum transverse area of the fourth ventricle was increased significantly in the case group (all P<0.05). The difference in distribution of the low, equal, and high signal in dentate nucleus between the 2 groups was statistically significant (χ²=43.114, P<0.001), and the difference in the maximum area of dentate nucleus between the 2 groups was not significant (P>0.05). The maximum width of the brachium pontis [odds ratio (OR)=3.327, 95% CI 1.454 to 7.615, P=0.004] and the maximum transverse area of the fourth ventricle (OR=0.987, 95% CI 0.979 to 0.995, P=0.002) were independent factors that distinguished cerebellar atrophy after epilepsy from the normal control, while the anterior-posterior diameter of pontine (OR=1.456, 95% CI 0.906 to 2.339, P>0.05) was not an independent factor that distinguished them. CONCLUSIONS In MRI imaging, cerebellar atrophy after epilepsy is manifested as significant atrophy of the brachium pontis, significant enlargement of the fourth ventricle, and increased dentate nucleus signaling while insignificant dentate nucleus atrophy. This particular pattern may be associated with seizures and exacerbated pathological processes.
Humans ; Magnetic Resonance Imaging ; Pons ; Epilepsy/diagnostic imaging* ; Atrophy/pathology* ; Cerebellum/pathology*